Grupo de Investigación BIOSALUD, Universidad de Caldas, Manizales, Colombia..
Published: August 2023
AI Article Synopsis
Article Abstract
Introduction: Drug resistance to azoles is a growing problem in the Candida genus.
Objective: To analyze molecularly the genes responsible for fluconazole resistance in Candida tropicalis strains.
Materials And Methods: Nineteen strains, with and without exposure to fluconazole, were selected for this study. The expression of MDR1, CDR1, ERG11, and ERG3 genes was analyzed in sensitive, dose-dependent sensitive, and resistant strains exposed to different concentrations of the antifungal drug.
Results: MDR1, ERG11 and ERG3 genes were significantly overexpressed in the different sensitivity groups. CDR1 gene expression was not statistically significant among the studied groups. Seven of the eight fluconazole-resistant strains showed overexpression of one or more of the analyzed genes. In some dose-dependent sensitive strains, we found overexpression of CDR1, ERG11, and ERG3.
Conclusion: The frequency of overexpression of ERG11 and ERG3 genes indicates that they are related to resistance. However, the finding of dose-dependent resistant/sensitive strains without overexpression of these genes suggests that they are not exclusive to this phenomenon. More basic research is needed to study other potentially involved genes in the resistance mechanism to fluconazole.
Candida auris is a growing concern due to its resistance to antifungal drugs, particularly amphotericin B (AMB), detected in 30 to 60% of clinical isolates. However, the mechanisms of AMB resistance remain poorly understood. Here we investigated 441 in vitro- and in vivo-evolved C.
Background And Aims: Inconsequential diseases can sometimes become extremely dangerous through mutation. Antifungal resistance has increased by 24%, and resistance only due to () species have increased by 60%. Here, we aimed to assess the knowledge of antifungal treatment and preventative measures to mitigate the consequences of infections caused by .
Unlabelled: exhibits innate resistance to azole antifungal drugs but also has the propensity to rapidly develop clinical drug resistance. Azole drugs, which target Erg11, is one of the major classes of antifungals used to treat infections. Despite their widespread use, the mechanism controlling azole-induced gene expression and drug resistance in has primarily revolved around Upc2 and/or Pdr1.
Candidiasis, a condition spurred by the unchecked proliferation of species, poses a formidable global health threat, particularly in immunocompromised individuals. The emergence of drug-resistant strains complicates management strategies, necessitating novel therapeutic avenues. Antimicrobial peptides (AMPs) have garnered attention for their potent antifungal properties and broad-spectrum activity against species.
Azole antifungals inhibit the sterol C14-demethylase (CYP51/Erg11) of the ergosterol biosynthesis pathway. Here we show that the azole-induced synthesis of fungicidal cell wall carbohydrate patches in the pathogenic mold Aspergillus fumigatus strictly correlates with the accumulation of the CYP51 substrate eburicol. A lack of other essential ergosterol biosynthesis enzymes, such as sterol C24-methyltransferase (Erg6A), squalene synthase (Erg9) or squalene epoxidase (Erg1) does not trigger comparable cell wall alterations.
